Shrinking pipelines and major cutbacks in CNS drug discovery in pharmaceutical companies have led to an increased awareness of the critical need for NIH-supported institutions to participate in early stage drug discovery research. NIH has initiated several strategic efforts to advance and de-risk novel therapeutic strategies by supporting early stage drug discovery that can providing data sets, proof-of-concept compounds, and in some cases drug leads or drug candidates that can be advanced towards clinical development in an industry setting. In addition to early stage drug discovery, this includes investments in discovery of clinical biomarkers and the advancement of novel molecules into clinical proof of concept studies. However, there are a number of challenges in establishing these new initiatives. Drug discovery is a unique and highly integrated discipline that has not traditionally been a major focus of NIH-supported institutions. For this reason, training of drug discovery scientists has not been a traditional focus of academic training programs. Instead, expertise and training in drug discovery occurs in pharmaceutical companies, where entry-level PhD scientists are trained across a broad range of disciplines that are key components of successful drug discovery research. For emerging efforts in academic drug discovery to succeed, it will be critical to provide outstanding training to equip young scientists with the skill sets required to build successful academic careers in which they incorporate aspects of drug discovery in their research or make drug discovery research a primary career focus. Vanderbilt has established world class academic CNS drug discovery program that utilizes the major infrastructure and expertise that is traditionally found only in industry settings. The program is enjoying tremendous success in driving fundamental advances in neuroscience and translational research through discovery and optimization of high quality research probes, drug leads, and clinical development candidates and using these tools to push the boundaries of our understanding of CNS systems that may be important for multiple brain disorders. This is providing our trainees with unique multidisciplinary and highly integrated CNS drug discovery training. We propose establishing a training program that builds on this success to systematically train postdoctoral fellows in multiple aspects of drug discovery research. Training opportunities include training in HTS and molecular pharmacology, medicinal chemistry, drug metabolism and pharmacokinetics, behavioral pharmacology, biomarker discovery, and other key sub disciplines that are critical for CNS drug discovery. Each project is pursued in a close collaboration between multiple laboratories in the program and provides an unprecedented opportunity for the highest level training in academic drug discovery. PUBLIC HEALTH RELEVANCE: We propose a comprehensive training program for postdoctoral trainees that will provide extensive training in CNS drug discovery research. Trainees will work in a unique training environment that is made possible through the combined resources and expertise of the Vanderbilt Program in Drug Discovery, along with collaborating departments and centers, including the Department of Pharmacology, Center for Molecular Neuroscience, Vanderbilt Institute for Imaging Science, among others. This program provides a unique opportunity for postdoctoral fellows to receive unprecedented training in multiple facets of CNS drug discovery research within the context of a highly integrated drug discovery environment led by highly accomplished drug discovery scientists.